Currently available evidence provides greater certainty of substantial net health benefit in pre-symptomatic MLD; evidence also suggests that individuals with early symptomatic disease benefit from treatment —

Using weighted analyses across all patient subpopulations, arsa-cel would achieve common thresholds for cost-effectiveness if priced between $2.3M – $3.9M —

— At the September 29 virtual public meeting, ICER’s independent appraisal committee will review the evidence, hear further testimony from stakeholders, and deliberate on the treatment’s comparative clinical effectiveness, other potential benefits, and long-term value for money —

BOSTON, September 14, 2023 – The Institute for Clinical and Economic Review (ICER) today posted its revised Evidence Report assessing the comparative clinical effectiveness and value of atidarsagene autotemcel (“arsa-cel”, Orchard Therapeutics) for metachromatic leukodystrophy (MLD).

“MLD is a devastating disease for children and their caregivers,” said ICER’s Chief Medical Officer, David Rind, MD. “It is extremely rare, and most doctors have never seen a case. Parent testimony shared throughout this report has provided a window into the hope and frustration that families are feeling as new treatments become available. With arsa-cel, we see a gene therapy again filling the promise of possible treatments for conditions that previously were untreatable.”

This Evidence Report will be reviewed at a virtual public meeting of the CTAF (CTAF) on September 29, 2023. The CTAF is one of ICER’s three independent evidence appraisal committees comprising medical evidence experts, practicing clinicians, methodologists, and leaders in patient engagement and advocacy.

A draft version of this report was previously open for a four-week public comment period. The updated Evidence Report and voting questions reflect changes made based on comments received from patient groups, clinicians, drug manufacturers, and other stakeholders. Detailed responses to public comments can be found here.

Key Clinical Findings

All childhood forms of MLD are rapidly progressive and eventually fatal.  We reviewed the clinical effectiveness of arsa-cel when compared to usual care for the treatment of three subpopulations of patients with MLD:

  • Presymptomatic late infantile subtype (LI-MLD)
  • Presymptomatic early juvenile form (EJ-MLD)
  • Early symptomatic EJ-MLD

The evidence demonstrates that:

  • The majority of presymptomatic LI and EJ-MLD patients who underwent arsa-cel therapy remained either asymptomatic or experienced mild symptoms.  We therefore conclude that for children with these forms of MLD we have high certainty of a substantial net health benefit (“A”).

  • For children with early symptomatic EJ-MLD evidence suggests that the magnitude and certainty of deriving benefit from treatment are lower, but there is high certainty that the treatment is better on average than usual care (“B+”). 

Key Cost-Effectiveness Findings

Arsa-cel has not yet been approved by the FDA, and the manufacturer has not announced a US price if approved. ICER has calculated a health-benefit price benchmark (HBPB) for arsa-cel to be between $2.3M – $3.9M

ICER’s HBPB is a price range suggesting the highest US price a manufacturer should charge for a treatment, net of all rebates and discounts, based on the amount of improvement in overall health patients receive from that treatment, when a higher price would cause disproportionately greater losses in health among other patients in the health system due to rising overall costs of health care and health insurance. In short, it is the top price range at which a health system can reward innovation and better health for patients without doing more harm than good.

About ICER

The Institute for Clinical and Economic Review (ICER) is an independent non-profit research institute that produces reports analyzing the evidence on the effectiveness and value of drugs and other medical services. ICER’s reports include evidence-based calculations of prices for new drugs that accurately reflect the degree of improvement expected in long-term patient outcomes, while also highlighting price levels that might contribute to unaffordable short-term cost growth for the overall health care system.

ICER’s reports incorporate extensive input from all stakeholders and are the subject of public hearings through three core programs: the California Technology Assessment Forum (CTAF), the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC), and the New England Comparative Effectiveness Public Advisory Council (New England CEPAC). These independent panels review ICER’s reports at public meetings to deliberate on the evidence and develop recommendations for how patients, clinicians, insurers, and policymakers can improve the quality and value of health care. For more information about ICER, please visit ICER’s website.